Methamphetamine modulates ACh-evoked currents in Xenopus occytes expressing the rat alpha7 receptors.
Although the cholinergic system is proposed to be involved in methamphetamine (MeAMPH)-induced abnormal behaviors, no direct evidence has been provided yet. The present study investigated the effects of MeAMPH on acetylcholine (ACh)-evoked currents in the neuronal nicotinic ACh receptors (alpha7) expressed in Xenopus oocytes. MeAMPH enhanced the currents in a time- and dose-dependent manner at concentrations ranged from 1 nM to 3 microM, reaching a maximum of 150% 30 min after treatment. Lesser potentiation was observed at higher concentrations (>3 microM) and instead, the currents were inhibited at more than 10 microM MeAMPH with a slow reverse after washing-out of the drug. The current potentiation or depression was caused via a pathway independent of G-protein, protein kinase C or cAMP-dependent protein kinase. The ACh dose-response curve was shifted to the left and to the right after treatment with 1 and 100 microM MeAMPH, respectively, suggesting that MeAMPH potentiated or inhibited ACh-evoked currents by a change in the affinity for ACh. The actions of MeAMPH on the neuronal nicotinic ACh receptors may represent a cellular mechanism for MeAMPH-induced abnormal behaviors and sensitization.
Nomura
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T
Department of Physiology, Kobe University School of Medicine, Japan.
Nishizaki
T
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*; D013449:Sulfonamides; D014981:Xenopus
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000109:Acetylcholine; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D008694:Methamphetamine; D011493:Protein Kinase C; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D013449:Sulfonamides; C070515:bisindolylmaleimide I; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide